Project Summary Current bone grafting techniques for functional rehabilitation with dental implants have limitations ? high- cost, difficulties with fixation and stabilization, insufficient bone regeneration, high morbidity using autogenous block grafts and prolonged healing of up to 9 months. Existing synthetic bone fillers cannot match defect shape and volume, are weakly resorbed (if at all), are not easily and quickly modifiable in size and shape during surgery, cannot promote early and enhanced neovascularization and osseointegration; and are poorly suited for advanced reconstruction. Current technologies cannot be modulated to match existing bone architecture ? a critical feature for improved healing. Although pre-implant reconstructive surgeries are commonly performed, an estimated 7% of patients are unable to receive dental implants due to these limitations. We propose to prove that our NuCressTM scaffold is a revolutionary advancement in bone healing and a transformational technology for dentists, periodontists and oral surgeons. We seek to prove in preclinical studies that dental implants or other bone regeneration treatments for tooth salvage treatments can be performed at a fraction of the cost and healing times required for today?s technologies. We propose to demonstrate the ability of our technology to support regeneration of mineralized tissues that recapitulate the mechanical, physical and biological properties of craniofacial bones and corresponding microenvironments, to facilitate improved dental implant success. We hypothesize that the NuCressTM scaffold technology will outperform currently available options in rabbit and canine bone regeneration models. After producing optimized scaffolds with enhanced porosity similar to calvarial bone, we will compare the NuCress? scaffold to a predicate and untreated control groups in models of critical sized calvarial defects, in an established sinus model, an established pre-clinical socket model, an established pre-clinical segmental defect model, and an established pre-clinical dental implant model. Successful Phase I and II SBIR studies will lead to first in human trials in dental implant patients and seek FDA approval to provide a superior option to facilitate improved dental implant success.! !